A new study from the Monell Center, the U.S.
Department of Agriculture (USDA), and collaborating
institutions reports a uniquely identifiable odor
signature from mouse models of Alzheimer’s disease.
The odor signature appears in urine before
significant development of Alzheimer-related brain
pathology, suggesting that it may be possible to
develop a non-invasive tool for early diagnosis of
Alzheimer’s disease.
“Previous research from the USDA and Monell has
focused on body odor changes due to exogenous
sources such as viruses or vaccines. Now we have
evidence that urinary odor signatures can be altered
by changes in the brain characteristic of
Alzheimer’s disease,” said study author Bruce
Kimball, PhD, a chemical ecologist with the USDA
National Wildlife Research Center (NWRC) who is
stationed at the Monell Center. “This finding may
also have implications for other neurologic
diseases.”
Identification of an early biomarker for Alzheimer’s
disease could potentially allow physicians to
diagnose the debilitating disorder before the onset
of brain decline and mental deterioration, paving
the way for upcoming treatments to slow early
progression of the disease.
Alzheimer’s is the most common form of dementia,
afflicting an estimated 5.1 million Americans over
the age of 65. There is no test to definitively
diagnose Alzheimer’s disease in living persons.
Although the progression of Alzheimer’s currently
cannot be stopped or reversed, an accurate diagnosis
can give patients and families time to plan for the
future and seek treatments for symptom relief.
“While this research is at the proof-of-concept
stage, the identification of distinctive odor
signatures may someday point the way to human
biomarkers to identify Alzheimer’s at early stages,”
said study author Daniel Wesson, PhD, a
neuroscientist at the Case Western Reserve
University School of Medicine.
In the study, published in the online journal
Scientific Reports, researchers studied three
separate mouse models, known as APP mice, which
mimic Alzheimer’s-related brain pathology.
Using both behavioral and chemical analyses, the
researchers found that each strain of APP mice
produced urinary odor profiles that could be
distinguished from those of control mice.
The odor changes did not result from the appearance
of new chemical compounds, but instead reflected a
relative shift of the concentrations of existing
urinary compounds.
The odor differences between APP and control mice
were mostly independent of age and preceded
detectable amounts of plaque build-up in the brains
of the APP mice. These findings suggest that the
characteristic odor signature is related to the
presence of an underlying gene rather than to the
actual development of pathological changes in the
brain.
Additional studies showed that the distinctive odor
profiles could be used to predicatively identify APP
mice versus control mice.
Because Alzheimer’s is a uniquely human disease,
scientists create models of associated brain
pathology to study the disease in mice. One of the
hallmark pathological indicators of Alzheimer’s
disease is an excess formation of amyloid plaque
deposits in the brain. Scientists mimic this
pathology in mouse models by introducing human genes
associated with mutations of the amyloid-β precursor
protein gene into the mouse genome. These genes are
then pharmacologically activated to make excess
amyloid-β protein, leading to plaque buildup in the
brains of APP mice.
Wesson and study co-author Donald Wilson of the
Nathan Kline Institute for Psychiatric Research and
New York University School of Medicine utilize the
mouse Alzheimer’s models to examine the role of
olfactory dysfunction as an early biomarker of
Alzheimer’s disease and other neurodegenerative
disorders.
The researchers note that extensive studies are
needed to identify and characterize
Alzheimer’s-related odor signatures in humans.
Research reported in the publication was supported
by grants from the National Institute on Deafness
and Other Communication Disorders and National
Institute on Aging (DC003906 and AG037693) of the
National Institutes of Health and from the Spitz
Brain Health Innovation Fund, Mt. Sinai Health Care
Foundation, and Alzheimer’s Association. The content
is solely the responsibility of the authors and does
not necessarily represent the official views of the
National Institutes of Health or other funders.
The NWRC has maintained a Field Station at Monell
for over 42 years. To date, more than 200
publications on bird and wildlife chemical senses
have resulted from the Monell-USDA affiliation,
disseminating information on the biology and
behavior of many animal and avian species, along
with knowledge to aid in effective management of
wildlife resources.
The National Wildlife Research Center is the
research arm of the U.S. Department of Agriculture’s
Wildlife Services program. It is the federal
institution devoted to resolving problems caused by
the interaction of wild animals and society. The
Center applies scientific expertise to the
development of practical methods to resolve these
problems and to maintain the quality of the
environments shared with wildlife.
See also
Britain's National Health Service approved trial for
dogs capable of sniffing out prostate cancer
(2015-08-31)
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For more information
Alterations of the volatile metabolome in mouse
models of Alzheimer’s disease
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Monell Chemical Senses Center
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